tbuckley/cabot-search huggingface dataset:
Deep learning model for predicting treatment response for patients with rectal cancer using 3D medical imaging.
Authors: June Hyuck Lim, Jaesung Heo, Jeongmin Park, Seonhwa Kim, Hanbyeol Jang
Journal: Journal of Clinical Oncology (2023)

168 Background: We developed a deep learning model to predict pathological response based on magnetic 3D resonance imaging in rectal cancer. Methods: A total of 242 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy followed by surgical resection were collected from single center. Surgical resection was performed at 6 to 8 weeks after the completion of preoperative CRT. Achieving pathogic complete response (pCR) was defined as complete absence of any tumour cells, in both the primary site and the dissected lymph node in surgical specimens. Based on pre-chemoradiotherapy T1-weighted axial 3D MR images, deep learning models were developed to predict pCR, respectively. Results: We analyzed 32,000 MRI images and involved several radiation oncologists in segmenation and classification. To calculate the probability of pCR using various convolutional neural network (CNN) architectures, several deep learning models were developed. The data input to the deep learning model was 3D MRI image, clinical data, and MRI metadata. Among 242 patients, 50 (20.7%) had evidence of pCR. The best model was developed based on SeResNet using transfer learning by MONA framework. The deep learning model showed an area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of 0.926, 0.831, 0.921, and 90.2% for predicting pCR. Conclusions: The pre-chemoradiotherapy T1-weighted 3D MR image-based deep learning model showed acceptable performance in predicting pCR in patients with rectal cancer.[Table: see text]
Predictive and prognostic features of metastatic colorectal cancer arising from the transverse colon: A pooled analysis of the CCTG/AGITG CO.17 and CO.20 randomized trials.
Authors: Joao Paulo Solar Vasconcelos, Nan Chen, Dongsheng Tu, Stephanie Yasmin Brule, Rachel Anne Goodwin, Derek J. Jonker, Timothy Jay Price, John Raymond Zalcberg, Malcolm J. Moore, Christos Stelios Karapetis, Lillian L. Siu, Jeremy David Shapiro, John Simes, Christopher J. O'Callaghan, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2023)

124 Background: Primary tumour location is predictive of anti-EGFR benefit and prognostic in metastatic colorectal cancer (mCRC). Transverse colon cancers are often categorized as right sided, but the optimal cut point is unclear. Canadian Cancer Trials Group (CCTG)/Australasian Gastro-Intestinal Trials Group ( AGITG) CO.17 compared Cetuximab (Cet) vs. best supportive care (BSC) in mCRC. CCTG/AGITG CO.20 studied the addition of Brivanib Alaninate to Cet in pre-treated KRAS wildtype (WT) mCRC. We investigated the predictive and prognostic features of transverse colon primary location in a pooled cohort from these trials. Methods: Data from patients with RAS WT mCRC from CO.17 and KRAS WT mCRC from CO.20 randomized to cetux were analyzed for treatment outcomes according to location - right, transverse and left. The cecum to transverse colon was considered right sided, while the splenic flexure to rectum was considered left sided. Results: 553 patients were included, 201 (36.3%) from CO.17 and 352 (63.7%) from CO.20. Primary site distribution was: 32 (5.8%) transverse, 101 (18.3%) right and 420 (75.9%) left. On multivariate analysis from 457 (82.6%) patients treated with Cet, left side was associated with superior OS (HR, 0.40; 95% CI, 0.24-0.68, p=0.0006) and PFS (HR, 0.48; 95% CI,0.29-0.79, p=0.004) compared to transverse colon. No significant difference was noted in OS (HR, 0.74; 95% CI, 0.41-1.31, p=0.30) and PFS (HR, 0.79; 95% CI, 0.46-1.36, p=0.40) between right side versus transverse colon. Sidedness was not associated with prognostic difference in OS or PFS in the 96 (17.4%) patients receiving BSC alone. Outcomes according to primary site and treatment are shown. Conclusions: Transverse mCRC has comparable prognostic and predictive features to right sided mCRC. In keeping with previous studies, left side was predictive of greater Cet benefit and presented better overall prognosis when single agent Cet was used after 5-FU, oxaliplatin and irinotecan. [Table: see text]
Reflex testing for RAS and BRAF mutations in metastatic colorectal cancer: A single Canadian academic oncology center experience.
Authors: Lena Cvetkovic, Lauren Said, Jean-Pierre M. Ayoub, Mustapha Tehfe, Marie Florescu, Bich Ngoc Nguyen, Danh Tran-Thanh, Geneviève Soucy, Richard Letourneau, Rasmy Loungnarath, Francine Aubin
Journal: Journal of Clinical Oncology (2023)

86 Background: Patients with left-sided metastatic colorectal cancer (mCRC) without mutations in RAS or BRAF V600E are eligible to a combination treatment of an anti-EGFR monoclonal antibody in association with chemotherapy. This combination is associated with a survival benefit and is recommended by oncology guidelines as first line therapy for RAS/BRAF wild type left-sided mCRC patients. The CHUM (University of Montreal Hospital Center) has implemented reflex testing of RAS/BRAF mutations for mCRC since October 22 nd 2019, and was one of the only hospitals in Canada to do so. With this study, we want to demonstrate that reflex testing of these mutations improves the quality of care received by patients. Methods: In this retrospective study, we reviewed pathological and clinical data of 101 patients with newly diagnosed mCRC that had their pathological diagnosis done at the CHUM. Patients diagnosed between July 1 st 2017 and October 21 st 2019, before implementation of reflex testing, (“Before reflex testing” group, n = 62 patients) were compared to patients diagnosed between October 22 nd 2019 and December 31 st 2021 (“After reflex testing” group, n = 39 patients). Results: The average delay between the mCRC biopsy and the result of the RAS/BRAF mutations was reduced to 25 days (CI95% 22.6 – 28.1) in the “After reflex testing” group, compared to 154 days (CI95% 111.2 – 202.5) in the “Before reflex testing” group. Respectively 66% (41/62) of patients in the “Before reflex testing” group and 69% (27/39) of patients in the “After reflex testing” received a systemic treatment. At initiation of systemic therapy, results of RAS/ BRAF mutations were available for 85% (35/41) of patients in the “After reflex testing” group, versus only 17% (7/41) of patients in the “Before reflex testing” group. Among patients eligible for an anti-EGFR monoclonal antibody and who received it, 100% of them (6/6) received it in the first line setting in the “After reflex testing” group, compared to 33% (3/9) in the “Before reflex testing” group. Conclusions: Our study shows that with reflex testing of RAS/ BRAF mutations, oncologists have quicker access to all relevant information to make the best treatment decision for their patients. It allows eligible patients to receive an anti-EGFR therapy in the first line setting, as recommended by oncology guidelines.
Does neoadjuvant treatment in resectable pancreatic cancer improve disease outcomes? Systematic review and metanalysis of randomized controlled trials.
Authors: Douglas Dias e Silva, Nicoly Marques Castro, Elivane da Silva Victor, Edna Terezinha Rother, Sergio Eduardo Alonso Araújo, Fernando Moura, Pedro Luiz Serrano Uson Junior
Journal: Journal of Clinical Oncology (2023)

704 Background: Neoadjuvant chemotherapy improves survival in borderline resectable pancreatic cancer (RPC). Whether these results are the same in upfront RPC is unknown. Methods: To evaluate the association of neoadjuvant treatment and outcomes in RPC a systematic review was performed including randomized trials of neoadjuvant treatment versus upfront surgery. Articles indexed in PubMed, Embase and Web of Science were evaluated. Data regarding treatment regimens, R0 rates, disease free survival (DFS) and overall survival (OS) were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Results: Of 3,229 abstracts, 6 randomized controlled trials were considered eligible with a combined sample size of 805 patients. Among the trials, the PACT-15, JSAP-05, and updated long-term results from PREOPANC and NEONAX trials were included. In the meta-analysis, we could see that neoadjuvant treatment in RPC does not improve DFS or OS; HR 0.72 [0.46-1.09] and HR 0.76 [0.52-1.11], respectively. Interestingly, R0 rates were improved about 20% with the neoadjuvant approach (HR 1.2 [1.04-1.37]). It is important to note that most studies evaluated gemcitabine-based regimens in the neoadjuvant setting. Conclusions: This metanalysis of six randomized controlled trials suggests that neoadjuvant chemotherapy with gemcitabine-based regimens does not improve PFS or OS in RPC compared to upfront surgery followed by adjuvant treatment. Neoadjuvant treatment improves R0 rates in about 20%. Randomized ongoing trials are eagerly waited with more active combined regimens including modified FOLFIRINOX.[Table: see text]
Identification and external validation of clinical-molecular features to predict benefit from oxaliplatin reintroduction/rechallenge in patients with refractory metastatic colorectal cancer (mCRC).
Authors: Francesc Salva, Rafael Paes, Matheus Costa e Silva, Heloisa Cruz, Nadia Saoudi Gonzalez, Iosune Baraibar, Javier Ros Montañá, Raquel Comas, Fiorella Ruiz-Pace, Ariadna Garcia, Renata Dalpino, Alexandre A. Jácome, Josep Tabernero, Elena Elez, Rodrigo Dienstmann
Journal: Journal of Clinical Oncology (2023)

153 Background: Oxaliplatin is a backbone cytotoxic treatment for mCRC patients, particularly in the front-line setting. In the refractory disease, current treatment options are scarce and with limited efficacy. Several retrospective studies have explored the efficacy of oxaliplatin reintroduction/rechallenge (OxRe) in this scenario. However, more evidence is still needed to determine which patients do benefit from this treatment strategy. Methods: The discovery cohort includes all patients treated with oxaliplatin in a third- or fourth-line setting at VHIO between 2015 and 2021 (N = 102). Results were externally validated in a real-world cohort of patients treated at community oncology practices from Oncoclínicas Group in Brazil (N = 157). We analyzed the impact of clinical-molecular features in uni- and multivariable prognostic models in terms of median progression free survival (mPFS) (discovery cohort) and median time to treatment discontinuation (mTTD) (validation cohort). For both cohorts separately, data was extracted from EHRs in structured formats (demographics, tumor characteristics, pharmacy records) and combined with elements from unstructured sources (physician notes on progression and survival status) using technology-based abstraction techniques. Results: In the discovery cohort, 102 out of 735 mCRC patients (13,9%) were eligible. Median oxaliplatin-free interval (from Oxl stop to OxRe) was 17 months (CI95% 13.0-23.2). In OxRe setting, mPFS was 4.0 months (CI95% 3.29-5.03). In PFS multivariate analysis, determinants of favorable outcome were left tumor location (p = 0.01), oxaliplatin-free interval (p = 0.03), administration of Bev in refractory setting (p = 0.001), and not receiving Bev in first-line treatment (p = 0.008). Overall, 27% of all patients had a mPFS &gt; 6 months with OxRe. In the validation cohort, out of 4,317 patients with mCRC, 157 (4%) were treated with OxRe. Median oxaliplatin-free interval was 15 months. Median time to treatment discontinuation (mTTD) of the OxRe was 3.4 months (CI95% 2.8-4.2). In multivariable model, the only independent prognostic factor was addition of Bev to OxRe (p = 0.036). Interestingly, 31% of all patients had mTTD &gt; 6 months, largely enriched (65%) in patients with first Bev exposure at the time of OxRe. Conclusions: This study suggests that in refractory mCRC patients re-exposed to oxaliplatin-based chemotherapy, the addition of Bev is associated with improved outcomes. One-third of the patients are long-term responders (PFS/TTD &gt; 6 months), reinforcing the value of this strategy in selected populations and the relevance of anti-angiogenic agents in refractory mCRC.
A phase II trial of hyperthermic intraperitoneal chemotherapy combined with tislelizumab and targeted therapy in high-risk hepatocellular carcinoma after R0 resection.
Authors: Sulai Liu, Zhihua Zhang, Yinghui Song, Yuhang Li, Weimin Yi, Bo Jiang, Chuang Peng
Journal: Journal of Clinical Oncology (2023)

TPS635 Background: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer, accounting for 75%–85% of cases, for which surgical resection represents the most effective treatment, with curative potential. However, the high incidence of tumor relapse (50%–70% 5 years after surgery) has hindered improved survival. Furthermore, early recurrence within 2 years after surgery accounts for 70% of relapsed HCC cases, is rarely treatable, and has been associated with poor survival. With the development of novel tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, no guidelines for novel systematic therapy to treat high risk of relapse HCC have been established. Targeted therapy combined with immunotherapy as systemic treatment has become a new approach in high risk of relapse HCC. Hyperthermic intraperitoneal chemotherapy (HIPEC), as an adjuvant treatment of abdominal malignant tumors, has achieved unique effects in the treatment of many cancers. The aim of this study was to assess the activity and feasibility of a combination of HIPEC with Tislelizumab and TKIs for the treatment of high risk of relapse HCC. Methods: The single-center, open-label, one-armed, Phase 2 study (NCT05546619) will enroll ~30 adults who meet the diagnostic criteria of high risk of relapse HCC (multiple tumors or satellite lesions; tumor diameter &gt; 5cm; HCC rupture and bleeding; combined with vascular invasion; AFP &gt; 32ng/ml). Patients will receive the following treatments as noted in the table. The primary and secondary endpoints are listed in the table. Tumor response will be evaluated once every 6 weeks for the first 48 weeks of treatment, and once every 12 weeks thereafter according to RECIST v1.1; safety will be assessed through monitoring the incidence and severity of adverse events graded according to CTCAE 5.0, vital signs and clinical laboratory results. Clinical trial information: NCT05546619 . [Table: see text]
Patient-specific tumor-informed circulating tumor DNA (ctDNA) assay to predict cancer recurrence in patients with resected pancreatic cancer.
Authors: Xiuchao Wang, Hongwei Wang, Xinyun Chen, Yuxiao Liu, Tiansuo Zhao, Song Gao, Jian Wang, Weidong Ma, Chuntao Gao, Jihui Hao
Journal: Journal of Clinical Oncology (2023)

744 Background: Pancreatic cancer (PC) is one of the leading causes of cancer death. Identifying molecular residual disease (MRD) with tailored tumor-informed ctDNA-based next-generation sequencing (NGS) assays after curative surgery could facilitate the individualized management of patients with resected pancreatic cancer (PC). Here, we prospectively evaluated the clinical performance of tumor-informed ctDNA mutation analysis using a novel Burning Rock Patient Specific Prognostic and Potential Therapeutic Marker Tracking (brPROPHET) approach for assessing MRD in patients with resected PC. Methods: The prospective cohort study recruited patients (n = 20) diagnosed with resectable stage I-III PC. Plasma samples (n = 63) were collected before surgery (baseline), 7-days after surgery (landmark), 30-days after surgery (before any adjuvant therapy), during the adjuvant therapy and follow-up. Individual tumors and matched white blood cells (WBCs) were whole-exome sequenced and somatic mutations were identified. Serial plasma samples were analyzed by a personalized, tumor-informed ctDNA-based NGS assay (brPROPHET) designed to target up to 50 variants per patient. Results: A total of 20 patients (stage I/II 10 [50%]/9[ 45%]) were analyzed. Patients were followed for a median of 190 days (range: 158 days to 396 days). Preoperative ctDNA was detected in 100% (20/20) of the patients. MRD status was analyzed postoperatively on day 7 and day 30 with a positivity rate of 11% (2/18) and 17% (2/12), respectively. Of the 4 patients with known recurrences, 2 had detectable ctDNA (50%, 2/4) at 7 days after surgery, whereas all disease-free patients were ctDNA-negative (100%, 13/13) at this time point. Detection at the landmark timepoint 7 days after surgery was associated with shorter recurrence-free survival (hazard ratio [HR]: 16.87, p=0.00363). The landmark negative predictive value (NPV) and positive predictive value (PPV) were 87.5% and 100%, respectively. When integrating all timepoints, 100% (4/4) of relapse patients were ctDNA positive before relapse, with the median leading time by brPROPHET assay to radiological recurrence was 126 days, whereas all of the patients with constant ctDNA negative status were disease-free (longitudinal PPV 80%, NPV 100%). In one relapsed patient who had elevated preoperative carbohydrate antigen (CA) 19-9 and constant normal postoperative CA19-9 (&lt;27 U/ml), ctDNA was detected prior to radiological relapse, with a lead time of 211 days. Conclusions: Patient-specific tumor-informed ctDNA-based postoperative monitoring predicts disease recurrence at earlier postoperative settings better than the clinical parameter CA19-9, which paves an alternative strategy in the individualized management of patients with resected PC.
Clinical development and evaluation of plasma angiogenesis factors from phase II study of FOLFIRI plus ramucirumab with recurrent colorectal cancer refractory to adjuvant chemotherapy with oxaliplatin/fluoropyrimidine (RAINCLOUD): RAINCLOUD-TR.
Authors: Tsuyoshi Hata, Naotoshi Sugimoto, Nobuyoshi Ohara, Masaaki Miyo, Shinichi Yoshioka, Yoshinori Kagawa, Atsushi Naito, Mitsuyoshi Tei, Hiroshi Tamagawa, Ken Konishi, Genta Sawada, Katsuki Danno, Toshio Shimokawa, Taroh Satoh, Norikatsu Miyoshi, Hidekazu Takahashi, Mamoru Uemura, Kohei Murata, Yuichiro Doki, Hidetoshi Eguchi
Journal: Journal of Clinical Oncology (2023)

173 Background: Higher levels of vascular endothelial growth factor-D (VEGF-D) is a potential predictive biomarker for ramucirumab (Ram) efficacy on overall survival and progression-free survival (PFS) in Ram+FOLFIRI vs Placebo+FOLFIRI for bevacizumab (Bev) refractory metastatic colorectal cancer (mCRC). However, it is not clear whether VEGF-D acts as a predictive biomarker in pts who pretreated without Bev. RAINCLOUD showed the clinical benefit of FOLFIRI+ plus Ram for pts with recurrent CRC refractory to adjuvant chemotherapy (median PFS was 6.2 months (M); ESMO-GI 2022). RAINCLOUD-TR was designed as a prospective biomarker study estimating the association of biomarkers with Ram efficacy. Methods: Plasma sample collections were done at time points of pre-/ post-treatments in pts receiving FOLFIRI+Ram. Measurements of 17 factors (including VEGF-A, VEGF-D and PlGF) were performed by multiplex assay with Luminex technology. The high/ low groups were defined bases on the median plasma level at the baseline. Results: From September 2017 to September 2021, 81 plasma samples were collected from 48 pts and 32 pts in both pre/ and post treatment. Level of VEGF-A, VEGF-D, PlGF and TSP-2 were all significantly higher in post vs pre-treatment [Table]. The ORR analyses were as follows; VEGF-A, VEGF-D and PlGF in low vs high were 50.0%/33.3% (p=0.35, HR 1.97), 55.0% /33.3% (p=0.22, HR 2.39), and 60.0%/28.6% (p=0.35, HR 1.95). The PFS analyses were as follows; VEGF-A, VEGF-D, and PlGF in low vs high were 6.1M/6.0M (p=0.815, HR 0.92), 7.6M /5.6M (p=0.095, HR 0.56), and 8.0M/4.2M (p=0.014, HR 0.40). In other factors, low TSP-2 were better ORR (low vs high: 66.7%/20.0% (p=0.004, HR 7.54) and PFS 7.5M/4.3M (p=0.022, HR 0.45). Conclusions: In this exploratory study, PFS was numerically greater for pts with low vs high VEGF-D for Ram in pts with mCRC pretreated without Bev. VEGF-D may not be predictive biomarker, but TSP-2 may be a potential prognostic biomarker, further studies in larger cohorts are needed to confirm our results. Clinical trial information: UMIN000028678 . [Table: see text]
Final analysis of a prospective controlled trial of the efficacy of uracil and tegafur/leucovorin for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).
Authors: Ken Kondo, Sotaro Sadahiro, Kazuhiro Sakamoto, Takashi Tsuchiya, Takao Takahashi, Hiroki Ohge, Toshihiko Sato, Yukata Ogata, Hideo Baba, Michio Itabashi, Masataka Ikeda, Madoka Hamada, Kiyoshi Maeda, Hiroyuki Masuko, Keiichi Takahashi, Junichi Sakamoto, Mitsuo Kusano, Ichinosuke Hyodo, Masataka Taguri, Satoshi Morita
Journal: Journal of Clinical Oncology (2023)

117 Background: The usefulness of adjuvant chemotherapy for stage II colon cancer with high-risk factors for recurrence has not been established. Methods: This was a prospective, non-randomized controlled study based on patients’ selection of treatment options, including randomized therapeutic decision-making. High-risk factors were defined as having at least one of the following factors: T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and &lt; 12 dissected lymph nodes. UFT (300 mg/m 2 /day) plus LV (75 mg/day) were orally administered for 6 months after surgery. The primary endpoint was disease-free survival (DFS) after adjusting for risk factors using propensity sore matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm. The secondary endpoints were overall survival (OS) and safety. Results: 1902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively between May 2012 and April 2016. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Eligible patients were divided into two groups: A, patients who selected surgery alone (n = 641); B, patients who selected UFT/LV treatment (n = 1239). Of the eligible patients, 402 in group A and 804 in group B were propensity score-matched. The 5-year DFS rate (95% confidence interval) was significantly higher in group B (76.3% [73.1-79.1]) than in group A (68.8% [63.9-73.2]) {hazard ratio [HR] 0.66 [0.51–0.84, P = 0.0008]}. The 5-year OS rates were not significantly different between group B and group A [HR 0.74 (95% CI 0.50–1.10, P = 0.1391)]. Using IPTW, significantly higher 5-year DFS [HR 0.71 (95% CI 0.59–0.86, P = 0.0006)] and overall survival [HR 0.66 (95% CI 0.49–0.90, P = 0.0122)] rates were observed in group B compared with group A. Multivariate analysis revealed that male sex, over 70 years old, T4, &lt; 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for recurrence. Conclusions: Adjuvant chemotherapy with UFT/LV significantly improves DFS. Oral UFT/LV as adjuvant chemotherapy shows efficacy with an acceptable safety profile for stage II colon cancer with risk factors. Clinical trial information: UMIN000007783 .